Malignant neoplasms have several characteristics which distinguish them from benign tumors and normal cells. These features include uncontrolled cell growth, invasiveness and metastasis. Malignant tumors may be differentiated from benign tumors or normal cells by morphological characteristics including anaplastic cells, increased mitotic index, abnormal mitotic cells, variable size and shape, increased nuclear to cytoplasmic ratio, and large prominent nucleoli. Much research has been focused on the biochemical and genetic characterization of malignant cells attempting to identify differences responsible for these phenotypic changes. Such studies have lead to the identification of so-called "oncogenes" which, if overexpressed or mutated, promote malignant transformation of cells.
Current agents which affect cellular proliferation are nonspecific cytotoxic agents such as DNA alkylating agents, DNA intercalators or microtubule depolymerizing agents. These agents all suffer from severe toxicities and lack of specificity towards the malignant cell. Thus, there is a long-felt need for molecules which effectively inhibit proliferation of malignant cells. Oligonucleotides designed to hybridize with nucleic acids encoding proliferation--associated proteins represent a novel approach to selectively inhibit gene expression, in particular expression of p120.